CROSS-IMMUNITY AS POSSIBLE PROTECTION AGAINST COVID-19

May 20, 2020: Vol 20 No 66

COVID-19 has devastated certain countries, such as the UK and the USA. COVID-19 seems to have relatively spared other countries, including India, and it is unclear whether lockdown is the only reason for this.

In a very important study, Grifoni et al (2020) studied T cell response to COVID-19 infection in nonhospitalized COVID-19 convalescent patients (n=20) and in unexposed individuals (n=20). The median age of the convalescent patients was 44 years; the sample was 45% male, and most patients had only mild illness (with mostly cough, fatigue, and fever). The median age of the unexposed sample was 31 years; this sample was 35% male. Blood from the unexposed sample had been drawn between 2015 and 2018, when the sample could not possibly have been exposed to SARS-CoV-2. All subjects were resident in the USA.

Important findings were:

1. In COVID-19 convalescent patients, CD4+ and CD8+ T cells were identified that were specific to the SARS-CoV-2 virus that is responsible for the disease. CD4+ cells were identified in 100% of the patients, and CD8+ in nearly 70% of the patients.

2. The CD4+ response to the SARS-CoV-2 spike protein was robust and correlated with the magnitude of the IgG and IgA titers against the virus.

3. Besides targeting the spike protein, CD4+ cells also targeted M and N viral proteins, and several other viral proteins, as well, including nsp and ORF proteins.

4. CD8+ cells targeted spike, M, and several ORF SARS-CoV-2 proteins.

5. Astonishingly, about 40-60% of persons who were unexposed to SARS-CoV-2 had CD4+ cells that were reactive against different viral proteins. In these persons, whereas reactivity against the non-spike proteins reached statistical significance, that against the spike protein narrowly missed statistical significance.

Summary

In this study, COVID-19 convalescent patients showed a robust CD4+ and CD8+ T cell response against spike, M, N, and other SARS-CoV-2 viral proteins. Importantly, about half of the sample that was unexposed to the SARS-CoV-2 virus had CD4+ lymphocytes that were reactive against the virus, suggesting that there may be cross-tolerance between the common cold coronaviruses and SARS-CoV-2.

Comments

1. There are 4 coronaviruses that cause the common cold in humans: HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-229E. Perhaps CD4+ cells against these viruses show cross-reactivity against SARS-CoV-2. This may explain why some persons and even some geographical areas seem to be relatively protected against COVID-19. Confirmation of this hypothesis would require study of T cell profiles in persons before exposure to SARS-CoV-2 and, again, after exposure to the virus. Such a study is not easily done!

2. Most of the COVID-19 vaccines under development target the spike protein with a view to amplify the CD4+ response against this protein. However, given that T cells in convalescent serum target other SARS-CoV-2 proteins, it may be desirable to include other antigens in the vaccine, as well.

Reference

Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM, Moderbacher CR, Rawlings SA et al. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell 2020; epub ahead of print.

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